Total Synthesis of Dixiamycins A and B via a Late-Stage N-N Bond Formation under Visible Light Photoredox Catalysis.

Intermolecular oxidative N-N bond formation reactions are quite challenging and are largely uncharted. N-N linked dimeric indolosesquiterpene alkaloids represent an underexplored class of natural products, and strategies for direct dehydrogenative N-N bond formation are limited. Here, we have reported that a late-stage visible-light photoredox catalysis facilitates N-N bond formation, leading to the total syntheses of atropo-diastereomers dixiamycins A () and B ().

Total Synthesis of (+)-7,7'-Bistaxodione via Late-Stage Electrochemical Dimerization.

The first asymmetric total synthesis of the tetraterpenoid (+)-7,7'-bistaxodione () via a unique late-stage electrochemical oxidative dimerization of a diterpenoid quinone methide tumor Inhibitor (+)-taxodione () has been described. The naturally occurring monomer was synthesized from aromatic abietane diterpenoid, ferruginol (1e) . Further, an efficient convergent synthetic route toward the naturally occurring aromatic abietane terpenoids has been shown via a Lewis acid-mediated diastereoselective cationic epoxy-ene cyclization.

Synthetic Approaches to Dimeric and Oligomeric Hexahydropyrrolo[2,3-b]indole Alkaloids.

Natural product synthesis has been the prime focus for the development of new chemical transformations and the drug discovery. The dimeric and oligomeric hexahydropyrrolo[2,3-b]indole alkaloids represent a architecturally intriguing class of cyclotryptamine alkaloids. These alkaloids share contiguous stereogenic centers with vicinal all-carbon quaternary stereogenic centers.

Total Synthesis of (+)- and (-)-Calycanthidine and Formal Synthesis of (-)-Idiospermuline via Key Pd(0)-Catalyzed Asymmetric Allylations.

We envisioned a novel asymmetric strategy to access unsymmetrically substituted dimeric 2-oxindoles [(,)- and (,)-] for the total synthesis of calycanthidine (). The key to success is the development of efficient Pd(0)-catalyzed asymmetric sequential allylations [via a highly enantioselective [up to 94% enantiomeric excess (ee)] and diastereoselective (up to ∼13:1) process] of unsymmetrically protected dimeric 2-oxindoles at the 3,3' position [such as (,)- and (,)-]. Gratifyingly, a mixture of bis-ester (±)-, ester-carbonates (±)- and (±)-, and bis-carbonate could afford (,)- and (,)- in highly stereoselective fashion, thereby culminating in the total synthesis of (+)-calycanthidine [-()] and (-)-calycanthidine ().

Asymmetric Synthesis of Taiwaniaquinone H via a Late-Stage Oxidative Decarboxylation.

The asymmetric syntheses of naturally occurring biologically relevant -abietane diterpenoids, (-)-taiwaniaquinone G (), and H () have been reported via a chiral pool strategy starting from commercially available abietic acid. A ring contraction of the middle ring of the [6,6,6]-carbotricyclic abietane diterpenoid core was carried out under the Wolff rearrangement. Finally, the synthesis of (-)-taiwaniaquinone H () was completed via a one-pot CAN-mediated oxidative decarboxylation.

Total synthesis of atropodiastereomers of heterodimeric alkaloids: narcipavline and narcikachnine.

We report the first asymmetric total synthesis of recently isolated heterodimeric alkaloids, narcipavlines A (1a) and B (1b), and narcikachnines A (2a) and B (2b), thereby confirming their absolute stereochemistry. These alkaloids showcase a unique heterodimeric structure, amalgamating two distinct types of alkaloids: the -hydrodibenzofuran containing tetracyclic galantamine core (6a) and the galanthindole core (7) featuring a biaryl axis. The presence of this biaryl axis, coupled with the substantial galantamine core (6a) at the substituents, imposes constraints on free rotation around the C-C axis, resulting in atropisomerism, an exceedingly rare phenomenon in nature.

Total Synthesis of (+)-Brevianamides A and B.

(+)-Brevianamides A () and B () are distinguished by their unique bicyclo[2.2.2]diazaoctane structure and have captured the interest of synthetic chemists due to their fascinating array of biological activities.

Total synthesis of bicyclomahanimbine by Cu(ii)-promoted photoredox process.

Since the isolation of carbazole alkaloids, the synthetic chemists have witnessed an upsurge in research of them due to their potential pharmacological properties. Our approach shows the total syntheses of five such biorelevant pyrano-[3,2]-carbazole alkaloids, emphasizing biomimetic and innovative synthetic methodologies such as cascade reactions and strategic bond formations through sustainable electrochemical and photochemical conditions.

Regioselective Electrochemical Construction of C-C Linkage at C5-C5' Position of 2-Oxindoles via an Intermolecular Anodic Dehydrogenative Coupling.

Applying electricity as a reagent in synthetic organic chemistry has attracted particular attention from synthetic chemists worldwide as an environmentally benign and cost-effective technique. Herein, we report the construction of the C-C linkage at the C5-C5' position of 2-oxindole utilizing electricity as the traceless oxidant in an anodic dehydrogenative homo-coupling process. A variety of 3,3-disubstituted-2-oxindoles were subjected to dimerization, achieving yields of up to 70 % through controlled potential electrolysis at an applied potential of 1.

Total synthesis of (-)-2-oxo epimesembranol and (+)-dihydromaritidine a key Johnson-Claisen rearrangement.

A general approach to alkaloids of the family following a key Johnson (orthoester)-Claisen rearrangement of an enantioenriched allylic alcohol has been disclosed. The tricyclic core (1c) of -3-octahydroindoline skeleton was achieved an ester-aminolysis followed by an intramolecular aza-Michael reaction with amine under elevated temperature. Utilizing aforementioned strategy, a collective total syntheses of alkaloids, such as (-)-2-oxo-epimesembranol (1d) [the first total synthesis], (-)-6-epimesembranol (1b), and (-)-mesembrine (1a) were shown.

Biomimetic total synthesis of the reported structure of (+)-selaginedorffone B.

The first enantioselective total synthesis of the reported structure of the structurally unique aromatic tetraterpenoid of anti-cancer potential, (+)-selaginedorffone B (2), has been accomplished from two modified abietane diterpenoids through an intermolecular Diels-Alder reaction between a bio-inspired diene 3 (HOMO counterpart) and dienophile 4 (corresponding LUMO counterpart) in a 23-step sequence, whereas the core framework of the monomeric abietane diterpenoid was constructed alkyne-activated ene-cyclization. Computational analysis was conducted to reveal the intricate regio and diastereoselectivity of this novel Diels-Alder reaction, strengthening the experimental results. The absolute configuration of the synthesized molecule was validated through X-ray studies of late-stage intermediates as well as comprehensive 2D NMR analysis.

Total Synthesis of (+)-Dixiamycin C via a Late-Stage Ni(II)-Photoredox -Arylation of Carbazoles.

We report the asymmetric total synthesis of dixiamycin C (1) through the shrewd alliance of the naturally occurring monomer xiamycin A methyl ester (5) and its bromo derivative (31) following a late-stage Buchwald-Macmillan's C-N bond formation via a photoredox electron transfer approach with a less reactive carbazole nitrogen. The key step in the synthesis of monomer xiamycin A methyl ester (5) involves Buchwald's Pd(II)-mediated aerobic dehydrogenative C-N bond formation, Beckmann rearrangement, and -acetylation of an electron-rich aromatic ring of an abietane core.

Concise Total Synthesis of (-)-Codeine.

Codeine and morphine are among the few natural products that are used directly as drugs for medical treatment. However, the availability of these is widely dependent on natural resources. Herein, we report an efficient enantioselective seven-step synthesis of (-)-codeine starting from simpler starting materials.

Total synthesis of (+)-oridamycins A and B.

We have accomplished a unified strategy to achieve the structurally intriguing indolosesquiterpene alkaloids with diverse biological activity, xiamycin A (1a), xiamycin A methyl ester (1b) and oridamycins A (2a), and B (2b), which possesses a complex 6/6/6/5/6-fused pentacyclic skeleton bearing a carbazole moiety fused with a highly functionalized -decalin motif. Lewis acid-mediated epoxy-ene cyclization establishes the required pentacyclic scaffold with the installation of the four contiguous stereogenic centers. Further oxidative cleavage of the vinyl functionality, followed by successive functional group interconversions, completed the total synthesis of the indolosesquiterpene alkaloids.

Total synthesis of naturally occurring abietane diterpenoids a late-stage Fe(iii)-TAML catalysed Csp-H functionalization.

The synthesis of diverse -fused decalins, including the abietane diterpenoids scaffold, using an efficient selective oxidation strategy is described. The abietane core was demonstrated to be a versatile scaffold that can be site-selectively functionalized. The utility of this novel oxidation strategy was showcased in a concise total synthesis of six abietane congeners.

Highly chemoselective oxidative dimerization of indolosesquiterpene alkaloids: a biomimetic approach to dixiamycin.

Dimeric indolosesquiterpene alkaloids, typically N-N- and C-N-linked xiamycin dimers, feature a pentacyclic framework with four contiguous stereogenic centers at the periphery of a -decalin scaffold to which a carbazole unit is attached. In comparison with actual biosynthetic dixiamycin derivatives, we designed C-C-linked xiamycin dimers, aiming to use them as a powerful tool to create unique scaffolds as drug candidates. In this work, we disclose the first synthetic route to access a C-C dimeric indolosesquiterpene skeleton, featuring a hypervalent iodine (PIFA)-catalyzed oxidative dimerization reaction in a single-step operation with overwhelming control over the chemoselectivity and regioselectivity.

Asymmetric Aldol Reactions Catalyzed by Polymeric Self-Assembly with Side-Chain Dipeptide Pendants.

To explore the role of proline amide moieties in polymer-supported organocatalysts, side-chain l-proline-l-alanine (Pro-Ala) dipeptide-containing block copolymers were synthesized, and their catalytic potential for the aldol reaction was explored. The dipeptide monomer (Boc-Pro-Ala-HEMA) was polymerized to prepare block copolymers in the presence of hydrophilic poly(poly(ethylene glycol) methyl ether methacrylate) () and hydrophobic poly(methyl methacrylate) () macro-chain transfer agents. Boc group expulsion from the block copolymers produced double hydrophilic () and amphiphilic () polymers.

Total Synthesis of (+)- and (-)-Calycanthine by Means of Thio-Urea-Catalyzed Sequential Michael Reactions of Bis-oxindoles.

A unified catalytic asymmetric approach to naturally occurring piperidinoindoline and pyrrololidinoindoline alkaloids has been realized via the development of a thio-urea-catalyzed sequential Michael addition of bis-oxindole onto nitroethylene (up to 93% ee and >20:1 dr). This strategy offers the total syntheses of either enantiomers of naturally occurring calycanthine.

Total Synthesis of Diterpenoid Quinone Methide Tumor Inhibitor, (+)-Taxodione.

An asymmetric polyene cyclization (92% ) strategy has been successfully applied for the first asymmetric total synthesis of oxidized abietane, anticancer agent, taxodione () sharing a -decalin system. Additionally, the total syntheses of pomiferin B () and gaultheric acid () (a -abietane) were achieved utilizing this unified approach.

Total synthesis of atropisomeric indolosesquiterpenoids N-N bond formation: dixiamycins A and B.

N-N dimeric indolosesquiterpene alkaloids constitute a class of under-investigated architecturally intriguing natural products. Herein, we report the first chemical oxidation approach to the asymmetric total syntheses of these atropisomeric indolosesquiterpenoids through N-N bond formation. Specifically, dixiamycins A (1a) and B (1b) were prepared through a Cu(i)-mediated aerobic dehydrogenative dimerization from the naturally occurring monomer xiamycin A methyl ester (2b); this preparation also represents the first total synthesis of dixiamycin A (1a).

Can postexercise hypotension also be observed in African and Asian populations: a systematic review and meta-analysis of randomized controlled trials.

Worldwide, raised blood pressure (BP) or hypertension is the global leading risk factor for the development of cardiovascular diseases and all-cause mortality, with the highest prevalence found in Asian and African origin populations. Post-exercise hypotension (PEH), defined as a sustained reduction in BP after a single bout of exercise is an important physiological phenomenon in BP management. However, little is known about the hypotensive effect of a single bout of exercise in non-Caucasian populations.

Total syntheses of naturally occurring antiviral indolosesquiterpene alkaloids, xiamycins C-F Csp-H functionalization.

Concise total syntheses of naturally occurring antiviral indolosesquiterpene alkaloids, xiamycin C (2a), D (2b), E (2c) and F (2d), have been achieved a late-stage oxidative δ-Csp-H functionalization of an advanced pentacyclic enone intermediate 8. This strategy takes advantage of -nitration of naturally occurring abietane diterpenoids to synthesize -bromo nitroarene derivative 11. A Suzuki-Miyaura coupling of 11 with phenylboronic acid followed by Cadogan's ring closure provided a modular approach to a carbazole ring required for a functionalized pentacyclic core of indolosesquiterpene alkaloids.

Asymmetric Total Syntheses of (-)-Lycoramine, (-)-Lycoraminone, (-)-Narwedine, and (-)-Galanthamine.

A concise asymmetric total synthesis of naturally occurring alkaloids sharing dihydrobenzofuran scaffolds, (-)-galanthamine (), (-)-lycoramine (), (-)-narwedine (), and (-)-lycoraminone (), is reported. Orthoester Johnson-Claisen rearrangement of allyl alcohol (+)- (98% ee) in diisopropylethylamine furnished enantioenriched cyclohexene (+)- (97.4% ee) with a quaternary stereogenic center.

Concise total syntheses of bis(cyclotryptamine) alkaloids thio-urea catalyzed one-pot sequential Michael addition.

Naturally occurring bis(cyclotryptamine) alkaloids feature vicinal all-carbon quaternary stereocenters with an elongated labile C-3a-C-3a' Sigma bond with impressive biological activities. In this report, we have developed a thio-urea catalyzed one-pot sequential Michael addition of bis-oxindole onto selenone to access enantioenriched dimeric 2-oxindoles with vicinal quaternary stereogenic centers at the pseudobenzylic position (up to 96% ee and >20 : 1 dr). This strategy has been successfully applied for the total syntheses of either enantiomers of chimonanthine, folicanthine, and calycanthine.

Electrocatalysis as a key strategy for the total synthesis of natural products.

Electrochemical strategies have been a powerful approach for the synthesis of valuable intermediates, in particular heterocyclic motifs. Because of the mild nature, a wide range of nonclassical bond disconnections have been achieved -generated radical intermediates in a highly efficient manner. In particular, anodic electrochemical oxidative strategies have been utilized for the total synthesis of many structurally intriguing natural products.